We request funds for a Q Exactive Plus mass spectrometer - liquid chromatography system (Thermo Scientific) for high-throughput analysis of proteins and small-molecules metabolites and for label-free and isobaric quantitation. Due to its potential for high impact on existing NIH-funded research programs and Centers, the University of Rochester Medical Center (URMC) has targeted proteomics as an area of critical development. The University's commitment to develop and support a Proteomics Core facility has been essential for improving the accessibility of mass spectrometry resources, services, and expertise to the research community. Mass spectrometry provides a powerful high-throughput analysis technique. It is used in many medical and biological sciences for discovery applications and in clinical or analytical screens that require large-scale target detection and quantification of complex protein mixtures. The requested Q Exactive Plus System is a versatile bench top instrument that excels at high-throughput and high-resolution applications, at a level far beyond the capabilities of the current mass spectrometers in our proteomics core facility. In this application, 10 major users and 5 minor users provide project descriptions that impact 14 NIH research grants totaling over $3.9 million, as well as an NSF career grant. The diversity of users highlights the importance of this technology and the unmet level of need that will be addressed by the instrument. The need for sensitive high-throughput, high-resolution mass spectrometry is growing in the Medical Center and College, which encompass over 45 departments and research centers and over 800 research laboratories. To ensure the highest level of access to proteomic and metabolomic technology and services, the requested instrument will be housed in the URMC Rochester Proteomics Core (RPC) facility. Two dedicated core staff members will run the instrument, and the core staff and core director will manage projects, provide consulting, analyze data, and assist users with data interpretation and processing. Data storage, analysis, and processing will be performed at the University of Rochester's Center for Integrated Research Computing (CIRC), which currently manages a 144-core processor server for the Proteomics Core facility. Institutional support and oversight will ensure that high-level mass spectrometry services are developed and accessible to the research community.